Our research on Peptide Nucleic Acids (abbreviated as PNAs) focuses on introducing chemical modifications that will make this class of molecules broadly useful to detect sequences of DNA and to suppress the expression of genes associated with disease. Unique DNA sequences are associated with diseases, pathogens, and many agents associated with bioterrorism. Detection of DNA from these agents can be employed as a method to detect their presence or absence. Our research involves the synthesis of a class of non-natural molecules (called PNAs) that bind to specific DNA sequences. We can design our molecules to bind to any sequence of DNA, and previously we have found that our molecules are extremely good at selective recognition of DNA associated with anthrax. During the past year, we have improved the chemistry to make our molecules, and have continued to refine our assay using our PNA molecules to detect anthrax DNA. We have also begun a program to extend the application of our PNA detection to the areas of tuberculosis, human papilloma virus, and HIV. PNAs are also useful as antisense and antigene molecules, however delivery into cells has been difficult. This past year we have continued our collaboration with researchers in the NCI and FDA examining the delivery of PNA to cells using an SV40 delivery system. We have identified the optimal conditions for delivery to cells, and we have shown that our PNAs are able to sensitize multidrug resistant cancer cells to chemotherapy. We intend to continue these studies in a mouse model system.